The long-range goals of this proposal are to determine the pathogenesis and clinical significance of the decreased bone mass which has recently been established to exist in patients with diabetes mellitus. Work carried out by Drs. L. Schneider and H. Schedl at the University of Iowa has shown that the alloxan-diabetic rat has an insulin-correctable decrease of intestinal calcium absorption, decreased plasma levels of the most important vitamin D metabolite (1,25(OH)2D), and secondary hyperparathyroidism. Therefore, we plan to investigate calcium absorption, vitamin D metabolism, and calcitonin and parathyroid hormone blood levels in diabetic man before and after treatment with insulin. We will examine the effects of both ideal plasma glucose control ("artificial pancreas") and routine outpatient control, with the aim of discovering whether or not current therapy can correct the potential defect in calcium metabolism. We do not know if the reduced bone mass in diabetes results in an increased susceptibility to fractures. Clearly, major fractures cause increased morbidity and mortality in diabetics. We therefore plan to use the unique resources of the Rochester-Olmsted Epidemiologic Project to determine age- and sex-specific incidence rates for Colle's, femoral neck and spinal compression fractures, in the years 1965-1976, for Rochester's nearly 100 diabetics. Comparison of rates with those for the nondiabetic population will establish whether or not diabetes mellitus is associated with increased fracture risk, either before or after the diagnosis of diabetes. The proposed research project will be supported by the extensive laboratory facilities and expertise of the Mineral Research and Diabetes Research Laboratories, and the Department of Medical Statistics and Epidemiology of the Mayo Medical School and Clinic. Definitive consultative arrangements have been made with the respective heads of these divisions.